Diversity and Evolution of Mycobacterium tuberculosis: Moving to Whole-Genome-Based Approaches

Abstract

Genotyping of clinical Mycobacterium tuberculosis complex (MTBC) strains has become a standard tool for epidemiological tracing and for the investigation of the local and global strain population structure. Of special importance is the analysis of the expansion of multidrug (MDR) and extensively drug-resistant (XDR) strains. Classical genotyping and, more recently, whole-genome sequencing have revealed that the strains of the MTBC are more diverse than previously anticipated. Globally, several phylogenetic lineages can be distinguished whose geographical distribution is markedly variable. Strains of particular (sub)-lineages, such as Beijing, seem to be more virulent and associated with enhanced resistance levels and fitness, likely fueling their spread in certain world regions. The upcoming generalization of whole-genome sequencing approaches will expectedly provide more comprehensive insights into the molecular and epidemiological mechanisms involved and lead to better diagnostic and therapeutic tools.

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…Deciphering tuberculosis transmission dynamics is crucial for the optimisation of local and global control measures and the early detection of MDR and XDR outbreaks. [142][143][144] Whole-genome sequencing also provides a robust system for differentiating clinical isolates into major lineages and sublineages using an accurate nomenclature framework, 75 paving the way for investigations of lineagespecific pathobiological characteristics.…”

Diversity and disease pathogenesis in Mycobacterium tuberculosis

“…The inevitable, and concerning, consequence is that the combination in highburden TB settings of elevated strain diversity, direct competition between genotypes, and strong drug pressure will drive the emergence of increasingly virulent drugresistant isolates with low to no short-term fitness costs. In some respects, the recent expansion of the Beijing family of strains (a sublineage of Lineage 2) in diverse geographic settings, and their association with drug resistance and hypervirulence in animal models, provides a cogent realization of these combined selective pressures [56].…”

Comparative Genomics of Mycobacteria: Some Answers, Yet More New Questions

“…Thus, before asking whether we can document different between strains in controlled, experimental infections, we need to ask whether the laboratory models we use address the epidemiologic observations of "success" in the field. Whether different strains have a different propensity toward drug resistance and whether this could impart fitness advantages in the face of antibiotic pressures are completely separate matters that are addressed in Niemann and Supply (2014).…”